title: Eribulin monotherapy versus treatment of physician's choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study.
abstract: BACKGROUND
  Treatments with survival benefit are greatly needed for women with heavily pretreated metastatic breast cancer. Eribulin mesilate is a non-taxane microtubule dynamics inhibitor with a novel mode of action. We aimed to compare overall survival of heavily pretreated patients receiving eribulin versus currently available treatments.
  
  
  METHODS
  In this phase 3 open-label study, women with locally recurrent or metastatic breast cancer were randomly allocated (2:1) to eribulin mesilate (1·4 mg/m(2) administered intravenously during 2-5 min on days 1 and 8 of a 21-day cycle) or treatment of physician's choice (TPC). Patients had received between two and five previous chemotherapy regimens (two or more for advanced disease), including an anthracycline and a taxane, unless contraindicated. Randomisation was stratified by geographical region, previous capecitabine treatment, and human epidermal growth factor receptor 2 status. Patients and investigators were not masked to treatment allocation. The primary endpoint was overall survival in the intention-to-treat population. This study is registered at ClinicalTrials.gov, number NCT00388726.
  
  
  RESULTS
  762 women were randomly allocated to treatment groups (508 eribulin, 254 TPC). Overall survival was significantly improved in women assigned to eribulin (median 13·1 months, 95% CI 11·8-14·3) compared with TPC (10·6 months, 9·3-12·5; hazard ratio 0·81, 95% CI 0·66-0·99; p=0·041). The most common adverse events in both groups were asthenia or fatigue (270 [54%] of 503 patients on eribulin and 98 [40%] of 247 patients on TPC at all grades) and neutropenia (260 [52%] patients receiving eribulin and 73 [30%] of those on TPC at all grades). Peripheral neuropathy was the most common adverse event leading to discontinuation from eribulin, occurring in 24 (5%) of 503 patients.
  
  
  CONCLUSIONS
  Eribulin showed a significant and clinically meaningful improvement in overall survival compared with TPC in women with heavily pretreated metastatic breast cancer. This finding challenges the notion that improved overall survival is an unrealistic expectation during evaluation of new anticancer therapies in the refractory setting.
  
  
  BACKGROUND
  Eisai.
authors.affiliation: Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona, Spain. c.j.twelves@leeds.ac.uk
authors.forename: Javier
authors.initials: J
authors.lastname: Cortes
authors.forename: Joyce
authors.initials: J
authors.lastname: O'Shaughnessy
authors.forename: David
authors.initials: D
authors.lastname: Loesch
authors.forename: Joanne L
authors.initials: JL
authors.lastname: Blum
authors.forename: Linda T
authors.initials: LT
authors.lastname: Vahdat
authors.forename: Katarina
authors.initials: K
authors.lastname: Petrakova
authors.forename: Philippe
authors.initials: P
authors.lastname: Chollet
authors.forename: Alexey
authors.initials: A
authors.lastname: Manikas
authors.forename: Veronique
authors.initials: V
authors.lastname: Diéras
authors.forename: Thierry
authors.initials: T
authors.lastname: Delozier
authors.forename: Vladimir
authors.initials: V
authors.lastname: Vladimirov
authors.forename: Fatima
authors.initials: F
authors.lastname: Cardoso
authors.forename: Han
authors.initials: H
authors.lastname: Koh
authors.forename: Philippe
authors.initials: P
authors.lastname: Bougnoux
authors.forename: Corina E
authors.initials: CE
authors.lastname: Dutcus
authors.forename: Seth
authors.initials: S
authors.lastname: Seegobin
authors.forename: Denis
authors.initials: D
authors.lastname: Mir
authors.forename: Nicole
authors.initials: N
authors.lastname: Meneses
authors.forename: Jantien
authors.initials: J
authors.lastname: Wanders
authors.forename: Chris
authors.initials: C
authors.lastname: Twelves
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D005663:Furans / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007659:Ketones / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy; D015996:Survival Rate; D000095662:Polyether Polyketides
chemical_list: D000970:Antineoplastic Agents; D005663:Furans; D007659:Ketones; C490954:eribulin; D000095662:Polyether Polyketides